Many proteins in nature contain copper in their active sites, and these sites are typically involved in redox catalysis performing a wide array biological functions such as electron carrier proteins (azurin, plastocyanin), oxygenase activity (tyrosinase, methane monooxygenase, galactose oxidase, cyctochrome c oxidase), and oxygen transport (hemocyanin). Specifically, type-3 copper sites contain 2 copper ions in close proximity and each copper is bonded to the protein backbone by three histidine nitrogens. These type-3 copper centers are capable of reversibly binding dioxygen (O2) for the purposes of dioxygen transport and the oxidation of organic and inorganic substrates. One especially important enzyme in the class of type-3 copper centers is tyrosinase. In mammals, the enzyme is involved in the biosynthetic pathway for the formation of melanin. The enzyme catalyzes the hydroxylation followed by a two electron oxidation of tyrosine to dopaquinone. Given this mammalian enzymatic function for tyrosinase, the enzyme has been linked to skin pigmentation abnormalities such as flecks and defects. In recent studies, the tyrosine enzyme has been linked to Parkinson disease and other neurodegenerative disease. As such, the tyrosinase enzyme is quite significant in medicine, agriculture, and industry. Given the important enzymatic function of tyrosinase, significant study has occurred although the intimate reaction details are still unknown. Generally, the mechanism is considered to occur through a m-h2:h2- peroxo-dicopper(II) species (SP). Although copper can exist in oxidation states of Cu(I), Cu(II), and Cu(III), Cu(III) is generally not considered to be biologically relevant due to its rather positive redox potential (ca. 500 mV vs. SHE), though these ideas preceded the characterization of Cu(III) in simple reactions of Cu(I) amine complexes with O2. Recent studies have implicated a substrate-binding induced rearrangement to an isomeric bis-m-oxo-dicopper(III) intermediate (O) that performs phenol oxidation with electronic and kinetic isotope parameters consistent with enzymatic values. However, these and most other studies in the field have used non-biologically relevant ligands such as pyridine, pyrazine, or alkyl protected imidazoles. This proposal aims to use ligands more biologically relevant ligands in model complexes through computational studies and spectroscopic investigations to probe the biological relevance of the Cu(III) oxidation state. Such findings of the biological relevance of Cu(III) would provide a complete paradigm shift in copper biochemistry (e.g. Fe(IV)-oxo intermediates for non-heme iron sites).